Mango fruit contain many bioactive compounds, some of which are transcription factor regulators. Estrogen receptor alpha (ERα) and beta (ERβ) are two regulators of gene transcription that are important in a variety of physiological processes andalso in diseases including breast cancer. We examined the ability of the mango constituents quercetin, mangiferin, andthe aglycone form of mangiferin, norathyriol, to activate both isoforms of the estrogen receptor. Quercetin and norathyrioldecreased the viability of MCF-7 breast cancer cells whereas mangiferin had no effect on MCF-7 cells. We alsodetermined that quercetin and mangiferin selectively activated ERα whereas norathyriol activated both ERα and ERβ.Despite quercetin, mangiferin and norathyriol having similar polyphenolic structural motifs, only norathyriol activated ERβ, showing that bioactive agents in mangoes have very specific biological effects. Such specificity may be important given the often-opposing roles of ERα and ERβ in breast cancer proliferation and other cellular processes.